Newly diagnosed early-to-mild dementia due to Alzheimer's Disease MedDRA version: 20.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Torecan
Product Name: Thiethlyperazine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: THIETHYLPERAZINE
CAS Number: 1420-55-9
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Immungenetics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For AD subject only: 1.Newly diagnosed (= 12 months) early-to-mild Alzheimer’s disease as classified by a Mini-Mental State Examination (MMSE) Score of 25-18 reconfirmed at screening 2.AD diagnosis confirmed by recommended examinations in accordance with German DGN/DGPPN S3 Guideline “Dementia” and to standard at the clinical unit by: -psychometric and cognitive tests -lumbar puncture in subjects with uncertain AD diagnosis following CNS imaging -Clinical Dementia Rating (global CDR) is 0.5 or 1. Memory box score must be at least 0.5. Isolated or predominant episodic memory deficit, manifested as memory performance in the Logical Memory subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale-III 1 SD below age adjusted norms, according to hospital standard) 3.AD subject has full legal competence according to investigator opinion 4.Ability to comply with requirements or cognitive and other testing for the entire length of the trial available For healthy volunteer: 5.Subject is a non-demented volunteer, based on the assessment of medical history, physical examination and clinically laboratory data at screening as determined by the Investigator For AD subject and healthy volunteer: 6.Age = 55 - = 75 years 7.Written informed consent to participate within this trial 8.Subject is on stable dose for at least 3 month prior to screening when receiving protocol-allowed concomitant medications at screening (e.g. acetylcholinesterase inhibitors, NMDA receptor antagonists) 9.For subject receiving anticholinergic agents, oral corticosteroids, propranolol, clonidine, antihistamines other than cetirizin and EBSTEL® a washout period of 4 weeks prior to screening must be completed. Concerning anticholinergic agents in Group 1a: only for high- to medium-potency anticholinergic agents a washout period of 4 weeks prior to screening must be completed. 10.Post-menopausal females (post menopausal amenorrhea for at least 2 years or surgically sterilized (hysterectomy), tubal ligation is not acceptable) 11.Male subjects with reproductive potential, and have not been surgically sterilized, that have been informed and agreed to that he and his partner must use a highly effective method of contraception (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1.CSF cut-off values identified during routine Neurochemical Dementia Diagnostics 2.History or evidence of other significant neurological disease of the Central Nervous System (such as Parkinson's disease, multi-infarct dementia, fronto-temporal dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, pro-gressive supra nuclear palsy, epilepsy, myasthenia gravis, subdural hematoma or multiple sclerosis) 3.History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities 4.Significant neuroimaging abnormalities, previously known or discovered on the MRI scan, including evidence of infection, infarction (> 3 mm in size), brain tumors (other than small meningiomas), or other focal lesions, multiple lacunas or lacunas in a critical memory structure or severe confluent microvascular disease (but not mild white matter changes, which are frequent with aging) 5.History or evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV) 6.Clinical relevant ECG findings, abnormalities, e.g. pro-arrhythmic potential/effects on QT interval (QTc >450 msec for males, >470 msec for females, confirmed by manual assessment of ECG parameters) 7.History of new cardiovascular event within the last 6 months 8.Resting sitting vital signs: Systolic blood pressure = 100 mmHg or = 165 mmHg, Diastolic blood pressure = 60 mmHg or = 100 mmHg, heart rate = 50 beats/min or = 90 beats/min 9. Clinically significant renal disease or insufficiency, including but not limited to creatinine value of >1.5 mg/dl 10.ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal laboratory range, or history of severe hepa-tobiliary disease (e.g. hepatitis B or C, or cirrhosis) without enzyme elevation 11.Positive tested for hepatitis B surface antigen (HBsAG) or hepatitis C virus/antibodies (anti-HCV) for the first time within the last 6 months prior to the Screening Visit 12.Positive tested for human immunodeficiency virus (HIV) at Screening Visit 13.Fasting triglycerides >2.5 times of the upper limit of normal 14.Uncontrolled diabetes (FBG > 150 mg/dl) 15.Coagulopathy or any kind of anti-coagulant therapy 16.Extrapyramidal syndrome 17.Elevation of prolactin, e.g. subject with prolactin-dependent breast cancer or pituitary tumor 18.History of severe psychiatric disease like psychotic disorder or current anxiolytic or neuroleptic therapy (for dementia-related or other psychiatric disorder) within the last 3 months of enrolment 19.Chronic depression or bipolar disorder or history of major depression within the past 2 years or history of any episode of treatment-resistant depression (requiring > 1 antidepressants, ECT etc.) 20.Significant history of alcohol abuse or drug abuse within the past 6 months (at the judgment of the investigator) 21.Current treatment with TEP or treatment up to 24 month prior to screening 22.Known incompatibility of TEP or phenothiazines 23.Subject is receiving the following treatment that may interact with TEP, e.g. adrenaline, tricyclic antidepressants, narcotics, bromocriptine, MAO inhibitors, CYP2D6 inhibitors, tramadol, pentetrazol, levodopa, anticonvulsants, medication causing extrapyramidal symptoms increases the likelihood of central nervous system side effects 24.Participation in a clinical trial involving another investigational drug within 4 weeks prior to screening visit 25.Wom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a significantly increased efflux of Amyloid beta peptides from the brain into the bloodstream in subjects with newly diagnosed (within last 12 months) early-to-mild dementia due to Alzheimer’s Disease vs. healthy volunteers that is expected to be caused by the ABCC1 transporter-stimulating effect of thiethylperazine.;Secondary Objective: 1.To assess the thiethylperazine dependent changes in cognition. 2.To determine plasma concentrations of thiethylperazine during therapy 3.To assess the safety and tolerability of thiethylperazine in newly diagnosed (within last 12 months) subjects with early-to-mild dementia due to AD and to compare this profile with the outcome of a control group of healthy volunteers 4.To investigate the effect of thiethylperazine on CSF levels of phosphoTau181 and total Tau in subjects with newly diagnosed (within last 12 months) early-to-mild dementia due to AD ;Primary end point(s): Group mean changes from baseline day 2 to day 5 for Group 1a and 1b in plasma Aß Group mean changes from baseline day 2 to day 55 for Group 2 in plasma Aß ;Timepoint(s) of evaluation of this end point: Aß endpoints assessed at the following timepoints: Group 1a and 1b: Day 2, 3, 4, 5 Group 2: Day 2, 3, 4, 5, 6, 7, 8, 9, 14, 21, 28, 35, 42, 49, 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics (PK) and pharmacodynamics (PD) of TEP after 26 mg and 52 mg daily doses in AD subjects and healthy volunteers Treatment-emergent Adverse Events (AEs) Treatment-emergent Serious Adverse Events (SAEs) Adverse Events leading to premature discontinuation of trial medication Treatment-emergent clinically relevant laboratory abnormalities Vital signs (heart rate, blood pressure) 12-lead ECG (overall rhythm analysis, heart rate, PQ, PR, QRS, QT, QTc, P wave) ;Timepoint(s) of evaluation of this end point: Pharmacokinetic and pharmacodynamic endpoints assessed at the following timepoints in Group 1a, Group 1b and Group 2, starting on day 2: Prior to TEP dosing and at 0,5, 1, 1,5, 2, 4, 6, 8, 12 and 24 hours following the first administration of TEP | — |
Countries
Germany
Contacts
Public ContactChairman
Immungenetics AG
Outcome results
None listed